Activation of FIS1 by CNR1 Promotes Mitochondrial Cleavage to Inhibit Malignant Progression of Osteosarcoma
The article explored the mechanism of CNR1 on the malignant progression of osteosarcoma cells.The changes of high and low CNR1 expression and long-term survival in tumor tissues were analyzed by bio-analysis;CNR1 overexpression lentivirus was used to infect osteosarcoma cells;CCK-8,scratch assay,clonogenic assay,Transwell cell invasion assay and flow apoptosis assay were used to detect the changes of osteosarcoma cells'proliferation,colony formation and invasion ability,as well as the level of apoptosis;transmission electron micros-copy was used,MitoSOX probe and immunoblotting to detect changes in mitochondrial morphology and function;and nude mice loaded tumor assay to verify the growth of CNR1 high-expression osteosarcoma cells in vivo.The results showed that CNR1 expression was up-regulated in osteosarcoma tissues,and the long-term survival rate of patients in the group with high CNR1 expression was significantly higher than that in the group with low CNR1 ex-pression;the immunoblotting confirmed that lentivirus infection successfully induced the high CNR1 expression in osteosarcoma cell lines;the high expression of CNR1 significantly inhibited osteosarcoma cells'proliferation,col-ony formation,and invasive ability and induced osteosarcoma cells'apoptosis;CNR1 activated FIS1 thereby caus-ing excessive mitochondrial cleavage and inducing mitochondrial pathway apoptosis;in tumor-bearing nude mice,CNR1 overexpression inhibited malignant progression of osteosarcoma cells by promoting mitochondrial pathway apoptosis.
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